Our long-term research goal is to elucidate the physiological role of histamine in the regulation of renal hemodynamics and renal function. In this proposal we describe experiments designed to test the hypothesis that histamine is the key modulator of renal vascular resistance in four autoregulatory events associated with renal hemodynamics: (1) maintenance of renal blood flow despite reductions in renal perfusion pressure (pressure autoregulation), (2) post-occlusion reactive hyperemia, (3) maintenance of renal blood flow during infusion of low doses of vasoconstrictors (norepinephrine and angiotensin II), and (4) maintenance of renal blood flow during low levels of renal nerve stimulation. Evidence that renal histamine participates in these four autoregulatory events will be determined by evaluating the ability of (a) infusion of histamine H1 and H2 receptor antagonists, (b) infusion of inhibitors of histamine release, and (c) infusion of inhibitors of histidine decarboxylase to compromise renal hemodynamic adjustments. In addition, we will measure the concentration of the amine in renal venous plasma to determine histamine "overflow" during evaluation of each of the autoregulatory manipulations. Finally, effects of each antihistamine drug on glomerular filtration rate and electrolyte excretion will be determined before and during reduction in renal perfusion pressure to 80 mmHg.